New Treatments on the Horizon
In another presentation, Nathan C. Steinle, MD, of California Retina Consultants, presented a study that assessed the durability of response to sozinibercept in patients with retinal vascular diseases. This novel therapeutic agent is designed to inhibit VEGF-C and VEGF-D in conditions where VEGF-A suppression alone is insufficient.
Sozinibercept was combined with standard anti–VEGF-A therapies such as ranibizumab or aflibercept. It involved a prospective, post hoc analysis of two phase 1b, open-label, dose-escalation studies, including 40 patients with neovascular age-related macular degeneration (nAMD; 31 patients) or diabetic macular edema (nine patients). These patients, either treatment-naive or previously treated, received three intravitreal injections of ranibizumab or aflibercept in combination with sozinibercept at various doses.
Results indicated that sozinibercept combination therapy was well tolerated, with no dose-limiting toxicities. In treatment-naive nAMD patients, the mean best-corrected visual acuity (BCVA) improved significantly from baseline at months 3 and 6. Previously treated nAMD patients also showed BCVA improvements, although to a lesser extent. For patients with persistent diabetic macular edema, switching to sozinibercept plus aflibercept resulted in notable BCVA gains. The mean time to requiring retreatment was longer in treatment-naive patients than in those previously treated, indicating a durable response.
“Combination therapy with sozinibercept is going to be really important,” said Dr. Lim, who was not involved in the study, “because it attacks with a dual mechanism of action.”
Oral agents promise a potentially easier alternative for patients compared with frequent injections. CU06-1004 is a novel orally administered endothelial dysfunction blocker that has shown promise in stabilizing damaged capillaries, reducing abnormal angiogenesis, and inhibiting inflammatory activation in preclinical studies. “CU06 is very interesting to me because by preventing endothelial loss, it gets to the pathophysiology of why the blood vessels break down,” Dr. Lim said.
In a proof-of-concept phase 2a, multicenter, open-label, parallel-group trial, investigators randomly assigned 67 patients with diabetic macular edema to receive 100 mg, 200 mg, or 300 mg of CU06-1004 once daily for 12 weeks, followed by a 4-week follow-up.
Results presented by Victor Gonzalez, MD, of Valley Retina Institute in Texas, indicated that the oral agent improved BCVA, stabilized central subfield thickness, and showed positive anatomical changes in optical coherence tomography images. CU06-1004 was well tolerated, with no drug-related serious adverse events.
“The number [of patients] was very small, and we will need a much longer, larger trial to see if [CU06-1004] has benefits long term,” said Dr. Boyer, who was not involved in the study. “But I think we’re all very excited if we can find an oral agent for treating diabetic retinopathy. It would be easier for the patient to take a pill than having to come in for injections.”
The sustained-release axitinib implant, OTX-TKI, is also generating significant interest, particularly for nonproliferative diabetic retinopathy. Axitinib, a tyrosine kinase inhibitor (TKI), targets signaling pathways crucial in cellular processes, providing a novel approach to managing diseases where traditional therapies might fall short. Unlike traditional anti-VEGF treatments that focus solely on cytokine levels, TKIs block the activation of signaling pathways, preventing downstream signaling regardless of cytokine levels. This mechanism is particularly important because it effectively inhibits disease progression even if levels of VEGF are high, Dr. Lim explained.
In the phase 1 HELIOS trial, OTX-TKI was assessed in patients with nonproliferative diabetic retinopathy. This multicenter, double-masked, parallel-group clinical study included 21 patients who had not received anti-VEGF treatment, dexamethasone intravitreal implants in the previous 12 months, or intraocular steroid injections in the prior 4 months. Patients were randomly assigned to receive either OTX-TKI or sham treatment.
Results presented by Dilsher S. Dhoot, MD, of California Retina Consultants, indicated that OTX-TKI was generally well tolerated, with no serious ocular adverse events. At 48 weeks, 46.2% of eyes treated with OTX-TKI showed a 1- or 2-step improvement on the Diabetic Retinopathy Severity Scale (DRSS) compared with none in the sham arm. Additionally, no eyes treated with OTX-TKI experienced a worsening on the DRSS, whereas 25% of eyes in the sham arm did. Vision-threatening complications, such as proliferative diabetic retinopathy or diabetic macular edema, developed in 37.5% of the sham group but in none of the OTX-TKI treated eyes. A single injection of OTX-TKI provided durable DRSS improvement for up to 48 weeks, with no patients in either arm requiring rescue therapy.
“This is a really exciting add-on treatment,” Dr. Lim said, who was not involved in the study. She explained that it is initially necessary to control the disease with standard treatments, because TKIs may take longer to exhibit their effects. Once the disease is stabilized, TKIs can be used alongside other therapies, potentially reducing the reliance on frequent anti-VEGF injections. “These are preliminary results, but that’s the hope going forward.”
Dr. Lim and Dr. Boyer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.